The field of the invention relates to a class of small molecule compounds that inhibit virus infection. Hepatitis C virus (HCV) is a human pathogen that primarily infects human hepatocytes and causes chronic liver diseases. It remains unclear whether direct-acting antiviral (DAA)-containing regimens fully prevent pathology or restore normal immunity. Moreover, with continuous and expanded usage of DAAs, HCV is expected to become progressively more drug resistant, thereby eroding the efficacy of DAAs. Lastly, most DAAs are hardly affordable to patients in resource-limited countries. For these reasons, druggable host targets and new lead compounds are highly desirable.
HCV entry is a multifaceted target for intervention. HCV encodes ten viral proteins to complete its life cycle. Viral glycoproteins E1 and E2 together form spikes on the viral envelope, which then engage with cell surface molecules and trigger the endocytosis of the viral particle. In addition, E2 interacts with HCV nonstructural protein 2 (NS2) and plays an important role in virus morphogenesis. Recent advances have suggested that HCV enters hepatocytes in a step-wise fashion by utilizing multiple cellular membrane proteins, including CD81, scavenger receptor BI (SRBI), claudin-1 (CLDN1), occludin (OCLN), epidermal growth factor receptor (EGFR), and cholesterol-uptake receptor Niemann-Pick C1-like 1 (NPC1L1). Further, the GTPase HRas acts as a signal transducer for EGFR-mediated HCV entry by regulating lateral membrane diffusion of CD81 which then enables tetraspanin receptor complex assembly.